CN1635861A - Medicine-containing polymer coated support - Google Patents

Abstract

A stent assembly comprising an expensible tubular supporting element and at least one coat of electrospun polymer fibers, each of the at least one coat having a predetermined porosity, the at least one coat including at least one pharmaceutical agent incorporated therein for delivery of the at least one pharmaceutical agent into a body vasculature during or after implantation of the stent assembly within the body vasculature.

Description

Drug-containing polymer-coated stent components

Field and Background of the Invention

The invention relates to an implantable stent, more particularly to a drug-containing polymer-coated stent assembly that can be implanted into blood vessels. The purpose of the stent is to deliver agents to surrounding tissue.

Coronary heart disease can develop narrowings that cause the arteries to narrow or narrow. Currently, percutaneous coronary intervention (PCI), including balloon angioplasty and stent deployment, is the mainstay of coronary heart disease treatment. Treatment of coronary artery disease often involves acute complications such as late restenosis due to coronary artery injury caused by angioplasty.

Restenosis refers to the reclosure of previously narrowed and subsequently dilated peripheral or coronary vascular tissue. Restenosis is caused by an incidental natural repair process. This natural repair process involves cell migration and proliferation in response to damage to the artery that is inevitably caused by angioplasty. In restenosis, this natural repair process continues, sometimes until the vessel is completely closed.

The general method to solve the problem of restenosis is to implant a stent in the coronary artery to provide a radial support to the coronary artery and prevent it from narrowing. However, clinical data show that stents usually do not prevent late restenosis of blood vessels, which begins about three months after angioplasty.

To date, many efforts have been made to address the problem of restenosis, including drug delivery and sometimes intravascular irradiation of arteries that have undergone angioplasty. But these efforts have not been successful. Therefore, current research efforts are gradually shifting to the local administration of various agents to the site of arterial injury caused by angioplasty. Advantages of such localized treatments include the possibility of achieving higher drug concentrations at the affected lesion site. An example of such a treatment is the local delivery of toxic agents such as taxol, rapamycin, etc. to vascular sites via a catheter delivery system. However, local therapeutic systems relying solely on "one-shot" administration are still not effective in preventing late restenosis.

Various attempts have been made to develop stents with local drug delivery, most of which are various so-called stent-grafts, i.e. a metal stent covered with anti-coagulant and/or anti-proliferative agents The polymeric skin of the medicament. The therapeutic effect of this stent-graft is based on the gradual breakdown of the biodegradable polymer under the action of erosive biological media and the release of the drug into the tissue in direct contact with the stent-graft. Agent-loaded polymers can be applied, for example, by spraying or dipping the stent-graft in a solution or melt of the agent as disclosed in US Patent Nos. 5,383,922; 5,824,048; 5,624,411; and 5,733,327. Another method of making drug-containing polymers is disclosed in US Patent Nos. 5,637,113 and 5,766,710, in which a prefabricated membrane is attached to the stent. Other methods known in the art include deposition of agents such as by photopolymerization, plasma polymerization, etc. as described in US Patent Nos. 3,525,745; 5,609,629 and 5,824,049.

Stent-grafts with fibrous polymer coatings advance the fabrication of porous coatings with better graftability and highly developed surfaces. US Patent No. 5,549,049 discloses a stent graft with a coating made of polyurethane fibers applied to the stent by a conventional wet spinning process. The agent is added to the polymer prior to the coating process.

A more promising stent coating method is the electrospinning technique. Electrospinning technology is a method of manufacturing ultrafine synthetic fibers that reduces the number of process steps required for the manufacturing process and improves the finished product in several ways. The use of electrospinning technology in stent coating can obtain more durable stent coatings with a wide range of fiber thickness (from tens of nanometers to tens of microns), and obtain unusual uniformity, smoothness, and compliance. Distribution of porosity along the cladding thickness. The scaffold itself does not promote normal cell invasion, so the disordered proliferation of cells in the metal grid of the scaffold will cause cell proliferation. When the stent is electrospun to coat a graft with a porous structure, arterial tissue in the area surrounding the stent-graft invades the micropores in the graft elements. Furthermore, stent coatings can be made from a wide variety of polymers with different biochemical and physico-mechanical properties. Numerous examples of electrospinning techniques for stent-graft fabrication can be found in US Patent Nos. 5,639,278; 5,723,004; 5,948,018; 5,632,772; and 5,855,598.

It is well known that electrospinning technology is quite sensitive to changes in the electrophysical properties and rheological properties of the solution used in the coating process. In addition, in order to achieve the therapeutic effect, a sufficient amount of the agent must be added to the polymer to achieve a sufficient concentration, which also reduces the efficiency of electrospinning. In addition, the addition of agents to the polymer also reduces the mechanical properties of the final coating, although this drawback is somewhat negligible for relatively thick films, but for sub-micron fibers. It is unfavorable for the formed film.

In addition to the problem of restenosis, percutaneous coronary intervention also involves the risk of damaging the vessel when the stent is implanted. This risk is more understandable when one considers the fact that the artery in the region where the stent is intended to disintegrate is a defective artery.

Arteriosclerosis, or hardening of the arteries, is a common condition that affects virtually all arteries in the body, including the coronary arteries. Atherosclerotic plaque adheres to the arterial wall and grows day by day, causing the lumen of the artery to gradually narrow and narrow. Appropriate methods for eradicating arterial narrowing include balloon angioplasty and/or stent deployment techniques. The latter refers to the delivery of a stent to a defective site inside the artery with a balloon catheter, generally called a stent delivery device, and then radially expands the stent with a balloon to dilate the site, thereby enlarging the arterial passage.

When the balloon and/or stent expands, it ruptures the plaque on the artery wall and produces debris, or debris, with sharp edges that cut into the tissue. This can cause internal bleeding and possible localized infection which, if not treated properly, can adversely affect other parts of the body.

Local infection in the region of the defective site within the artery is not amenable to treatment with antibiotics injected into the patient's bloodstream, as such treatment is usually ineffective for local infection. A more general approach to this problem is to coat the metal mesh of the stent with a therapeutic agent that is in direct contact with the affected area. As noted above, this is a "prime-on-the-fly" approach, which, while shocking the infection, requires antibiotics and antibiotics given over a period of hours, days, or even months. / or other pharmaceuticals.

The risk of vessel damage during stent implantation can be reduced by using a soft stent that improves the biological interface between the stent and the artery thereby reducing the risk of arterial injury during stent implantation. Descriptions of polymer scaffolds or scaffolds coated with biocompatible fibers can be found in US Patent Nos. 6,001,125; 5,376,117; and 5,628,788. All of these patents are incorporated herein by reference.

US Patent No. 5,948,018 discloses a graft comprising an expandable stent element covered with a highly elastic polymeric graft element. Due to the high extensibility of the graft element, it does not limit the expansion of the stent. The graft element is manufactured by electrospinning technology to obtain the required porosity, which is conducive to the normal growth of cells. However, this US Patent No. 5,948,018 is silent on the damage caused by the stent during implantation into the complex tissue of the artery. This damage can lead to local infection or other disease at the implant site, which can negate the benefits of stenting unless properly managed.

Other related prior art includes: "Percutaneous Polymeric Stents in Porcine Coronary Arteries" of Murphy et al., Circulation86:1596-1604, 1992; "Dose Heparin Release Coating of the Wallstent limit Thrombosis and Platelet Deposition?" of Jeong et al., 92: Circulation 173A, 1995; and "Intercoronary Irradiation Markedlly Reduces Necintimal Proliferation after Balloon Angioplasty in Swine" by Wiedermann S.C., Amer. Col. Cardiol. 25:1451-1456, 1995.

Accordingly, it is generally recognized that there is a need to provide an efficient and reliable stent assembly with a drug-containing polymer coating, which can be implanted into a blood vessel for delivery of a drug to surrounding tissue without the various limitations described above. However, the use of this bracket assembly will bring great benefits.

Summary of invention

In accordance with one aspect of the present invention, a stent assembly is provided comprising an expandable tubular support and at least one electrospun polymeric fiber coating, each of the at least one coating being having a predetermined porosity, and wherein at least one of the coatings includes at least one agent introduced into the coating for the purpose of encapsulating the at least one A pharmaceutical agent is delivered into the vasculature of the body.

According to another aspect of the present invention, there is provided a method of manufacturing a stent assembly comprising: (a) electrospinning a first liquefied polymer onto an expandable tubular support such that the tubular support There is a first coating layer on the piece, and the first coating layer has a predetermined porosity; (b) introducing at least one medicament into the first coating layer.

According to still another aspect of the present invention, a method for treating narrowing of blood vessels is provided. The method of treatment includes deploying a stent assembly comprising an expandable tubular strut and at least one electrospun polymeric fiber coating into a constricted vessel, the at least one coating Each of the layers has a predetermined porosity, and at least one of the coating layers includes at least one agent introduced in the coating layer for the purpose of implanting the stent assembly in the vasculature of the body The at least one agent is delivered into the vasculature of the body during or after implantation.

According to yet another aspect of the present invention, a method of dilating a constricted blood vessel is provided. The method includes: (a) providing a stent assembly comprising an expandable tubular support and at least one electrospun polymeric fiber coating, the at least one coating having each having a predetermined porosity, and wherein at least one of the coatings includes at least one agent introduced within the coating; (b) deploying the stent assembly to the constricted region of the constricted vessel and (c) radially expanding the stent assembly within the vessel to expand the constricted region and allow blood to flow through the vessel.

According to yet another aspect of the present invention, a method for covering a medical implant implantable in a human body is provided. The method comprises: (a) electrospinning a first liquefied polymer onto a medical implant such that the medical implant bears a first coating having a predetermined porosity; (b) introducing at least one medicament into the first coating layer, thereby obtaining a coated medical implant.

According to still further features in preferred embodiments of the invention described below, said at least one agent is premixed with the liquefied polymer prior to electrospinning, whereby said at least one agent is introduced into the The steps are performed with electrospinning.

According to still further features in the described preferred embodiments the medical implant is selected from the group consisting of grafts, patches and valves.

According to still further features in the described preferred embodiments the at least one pharmaceutical agent is dissolved in the liquefied polymer.

According to still further features in the described preferred embodiments the at least one pharmaceutical agent is suspended in a liquefied polymer.

According to still further features in the described preferred embodiments the use of the at least one medicament is the treatment of at least one disease within a blood vessel.

According to still further features in the described preferred embodiments, the at least one disease comprises damage to vascular tissue during implantation of the stent assembly.

According to still further features in the described preferred embodiments the at least one disease is selected from restenosis and in-stent stenosis.

According to still further features in the described preferred embodiments the at least one disease is cellular hyperproliferation.

According to still further features in the described preferred embodiments the at least one coating and the at least one agent are designed and configured to provide a desired duration of delivery.

According to still further features in the described preferred embodiments the delivery is by diffusion.

According to still further features in the described preferred embodiments, the delivery begins upon radial expansion of the at least one coating layer caused by expansion of the expandable tubular support.

According to still further features in the described preferred embodiments the at least one covering layer comprises an inner covering layer and an outer covering layer.

According to still further features in the described preferred embodiments the inner cladding comprises a layer lining the inner surface of the expandable tubular support.

According to still further features in the described preferred embodiments the outer cladding comprises a layer overlying an outer surface of the expandable tubular support.

According to still further features in the described preferred embodiments the at least one medicament is comprised of particles embedded within polymer fibers produced in an electrospinning process.

According to still further features in the described preferred embodiments the step of introducing at least one agent into the first coating comprises constituting the at least one agent as a compact and distributing the compact on the polymer fibers In between, the polymer fibers are produced in an electrospinning process.

According to still further features in the described preferred embodiments the compact is a capsule.

According to still further features in the described preferred embodiments the compact is in powder form.

According to still further features in the described preferred embodiments the distribution of the compacts is effected by spraying.

According to still further features in the described preferred embodiments the expandable tubular support comprises a deformable mesh comprised of stainless steel wires.

According to still further features in the described preferred embodiments the cladding is of tubular construction.

According to still further features in the described preferred embodiments the method further comprises loading the tubular support onto a rotating mandrel.

According to still further features in the described preferred embodiments the method further comprises electrospinning a second liquefied polymer onto the mandrel to provide an inner cladding.

According to still further features in the described preferred embodiments the method further comprises electrospinning at least one auxiliary liquefied polymer onto the first coating, thereby forming at least one auxiliary coating.

According to still further features in the described preferred embodiments the method further comprises providing at least one adhesive layer on the tubular support.

According to still further features in the described preferred embodiments the method further comprises providing at least one adhesive layer on at least one coating layer.

According to still further features in the described preferred embodiments the adhesive layer is an impermeable adhesive layer.

According to still further features in the described preferred embodiments the adhesive layer is provided by electrospinning.

According to still further features in the described preferred embodiments, the electrospinning step comprises: (1) charging the liquefied polymer to produce a charged liquefied polymer; (2) placing the charged liquefied polymer in a first in an electric field; and (3) distributing the charged liquefied polymer in the direction of the mandrel in the first electric field.

According to still further features in the described preferred embodiments the mandrel is made of an electrically conductive material.

According to still further features in the described preferred embodiments the first electric field is defined between the mandrel and a distribution electrode at a first potential relative to the mandrel.

According to still further features in the described preferred embodiments the method further comprises providing a second electric field bounded by an auxiliary electrode at a second potential relative to the mandrel, the second The function of the electric field is to modify the first electric field.

According to still further features in the described preferred embodiments the auxiliary electrode functions to reduce inhomogeneity of the first electric field.

According to still further features in the described preferred embodiments the auxiliary electrode functions to control the fiber orientation of the respective coating layers.

According to still further features in the described preferred embodiments the mandrel is made of insulating material.

According to still further features in the described preferred embodiments the tubular support acts as a mandrel.

According to still further features in the described preferred embodiments the first electric field is defined between the tubular support and a distribution electrode at a first potential relative to the tubular support.

According to still further features in the described preferred embodiments the method further comprises providing a second electric field bounded by an auxiliary electrode at a second potential relative to the tubular support, the The second potential is used to modify the first electric field.

According to still further features in the described preferred embodiments the first liquefied polymer is a biocompatible liquefied polymer.

According to still further features in the described preferred embodiments the first liquefied polymer is a biodegradable liquefied polymer.

According to still further features in the described preferred embodiments the first liquefied polymer is a biostable liquefied polymer.

According to still further features in the described preferred embodiments the first liquefied polymer is a combination of a biodegradable liquefied polymer and a biostable liquefied polymer.

According to still further features in the described preferred embodiments the second liquefied polymer is a biocompatible liquefied polymer.

According to still further features in the described preferred embodiments the second liquefied polymer is a biodegradable liquefied polymer.

According to still further features in the described preferred embodiments the second liquefied polymer is a biostable liquefied polymer.

According to still further features in the described preferred embodiments the second liquefied polymer is a combination of a biodegradable liquefied polymer and a biostable liquefied polymer.

According to still further features in the described preferred embodiments each of said at least one additional liquefied polymer is independently a biocompatible liquefied polymer.

According to still further features in the described preferred embodiments each of said at least one additional liquefied polymer is independently a biodegradable liquefied polymer.

According to still further features in the described preferred embodiments each of said at least one additional liquefied polymer is independently a biostable liquefied polymer.

According to still further features in the described preferred embodiments each of said at least one additional liquefied polymer is independently a combination of a biodegradable liquefied polymer and a biostable liquefied polymer.

According to still further features in the described preferred embodiments the at least one agent is heparin.

According to still further features in the described preferred embodiments said at least one agent is a radioactive compound.

According to still further features in the described preferred embodiments the at least one agent is silver sulfadiazine.

According to still further features in the described preferred embodiments the method further comprises heating the mandrel before, during or after electrospinning.

According to still further features in the described preferred embodiments the method of heating the mandrel is selected from external heating and internal heating.

According to still further features in the described preferred embodiments the external heating is performed with at least one infrared radiator.

According to still further features in the described preferred embodiments said at least one infrared radiator is an infrared light bulb.

According to still further features in the described preferred embodiments the internal heating is performed with a built-in heater.

According to still further features in the described preferred embodiments the built-in heater is a built-in resistive heater.

According to still further features in the described preferred embodiments the method further comprises removing the stent assembly from the mandrel.

According to still further features in the described preferred embodiments the method further comprises immersing the stent assembly in a vapor.

According to still further features in the described preferred embodiments the method further comprises heating the vapor.

According to still further features in the described preferred embodiments the vapor is a saturated DMF vapor.

According to still further features in the described preferred embodiments the method further comprises exposing the stent assembly to a partial vacuum.

The present invention successfully overcomes the disadvantages of existing known stent structures by providing a stent assembly and its manufacturing method. The stent assembly of the present invention has performance characteristics that far exceed those of previous stent assemblies.

Brief introduction to the drawings

The invention will now be described, by way of example only, with reference to the accompanying drawings. When specifically referring to the details of the accompanying drawings, it is emphasized here that the purpose of the specific configuration shown in the drawings by way of example is only to illustrate and discuss the preferred embodiments of the present invention, and what is shown is only the principle of the present invention and conceptual content that I believe to be the most useful and understandable. The content presented here is necessary for the reader to have a basic understanding of the present invention, and does not intend to introduce the structure of the invention in more detail. How to practice the invention in several forms will become apparent to those skilled in the art from the description taken in conjunction with the accompanying drawings.

In the attached picture:

Figure 1 is a cross-sectional view of a bracket assembly according to the present invention;

Figure 2a is an end view of a bracket assembly according to the present invention;

Figure 2b is an end view of a stent assembly according to the present invention, the stent assembly further comprising at least one adhesive layer;

Figure 3 shows a tubular support designed and constructed to dilate narrowed blood vessels in the vasculature of the body;

Figure 4 is a partial view of a tubular support comprising a deformable wire screen;

Fig. 5 shows the situation that a stent assembly manufactured by the technology of the present invention is located in the arterial defect site;

Figure 6 shows a partial view of a nonwoven web of polymer fibers used to make at least one coating according to the present invention;

Figure 7 is a partial view of a nonwoven web of polymeric fibers including an agent consisting of compacts distributed between electrospun polymeric fibers;

Figure 8 shows a typical prior art electrospinning device;

Figure 9 shows an electrospinning device according to the present invention, which device also includes an auxiliary electrode;

Figure 10 shows an electrospinning device, which includes an electrostatic sprayer, two pumps and two baths;

Figure 11 shows an electrospinning apparatus that includes a drug-loaded supply, an electrostatic sprayer, and a conical deflector.

DESCRIPTION OF THE PREFERRED EMBODIMENT

1. The present invention relates to a stent assembly, which can be used to treat diseases in blood vessels. In particular, the present invention can be used to dilate narrowed blood vessels and deliver one or several agents into the vasculature of the body.

The principle and operation of the bracket assembly of the present invention can be better understood through the following description combined with the accompanying drawings.

Before describing at least one embodiment of the present invention in detail, it is pointed out here that the content about the detailed construction and layout of each element stated in the following description and drawings does not limit the present invention. The invention is capable of other embodiments or of being carried out in numerous ways. In addition, it should be pointed out that the words and terms used herein are only for convenience of description, and should not be construed as limiting the present invention.

Now look at the attached picture. Figure 1 shows a stent assembly according to a preferred embodiment of the present invention. The stent assembly includes an expandable tubular support 10 and at least one cladding layer 12 with a predetermined void ratio. According to this preferred embodiment of the invention, at least one cladding layer 12 comprises an inner cladding layer 14 lining the inner surface of the tubular support 10 and an outer cladding layer covering the outer surface of the tubular support 10 16. Figure 2a shows an end view of the stent assembly showing a tubular support 10 covered on the inside with an inner cladding 14 and outside with an outer cladding 16. Fig. 2b is also a top view of the stent assembly, wherein at least one covering layer 12 also includes at least one adhesive layer 15 for bonding the various components of the stent assembly. The preparation method of the adhesive layer 15 will be described in detail below.

According to a preferred embodiment of the present invention, at least one coating layer comprises at least one medicament introduced in the layer, the purpose of which is to deactivate the at least one stent assembly during or after implantation in the body's vasculature. The drug is delivered into the vasculature of the body. The use of the medicament is to treat at least one disease in a blood vessel.

Figure 3 shows a tubular support 10 designed and constructed to dilate narrowed blood vessels in the vasculature of the body. The tubular support 10 is radially expandable to dilate narrowed blood vessels. According to a preferred embodiment of the present invention, suitable configuration of the tubular support 10 and the at least one cladding layer 12 allows for such expandability of the stent assembly. The configuration of the tubular support 10 will first be described with reference to FIG. 4 , while the configuration of the at least one covering layer 12 will be described later.

FIG. 4 shows a partial view of the tubular support 10 . The support 10 includes a deformable wire mesh 18 which may be, for example, a deformable stainless steel wire mesh. Therefore, when the stent assembly is placed at a desired position in the artery, the tubular support 10 can radially expand to significantly expand the arterial tissue around the stent assembly, thereby eradicating the obstruction of blood flow in the artery. Expansion of the tubular support 10 can be accomplished by any means known in the art, for example, using a balloon catheter, or fabricating the tubular support 10 from a material exhibiting temperature-activated shape memory properties such as Nitinol.

The tubular support 10 is covered with at least one cladding layer 12 made of polymeric non-woven fibers by the electrospinning technique described in more detail below. According to this preferred embodiment of the invention, the polymer fiber is a highly elastic polymer fiber. The polymer fibers stretch as the tubular support 10 expands radially. Referring now again to FIG. 1, in a preferred embodiment of the present invention, at least one cladding layer 12 comprises an inner cladding layer 14 and an outer cladding layer 16, both of which are co-extensible with the expansion of the tubular support 10, That is, the tubular support 10 is substantially covered. In other embodiments of the present invention, the inner cladding layer 14 and/or the outer cladding layer 16 may be shorter in length than the tubular support 10, in which case the tubular support 10 is exposed at least at one end. In other embodiments of the present invention, the inner cladding layer 14 may not be provided.

Figure 5 shows a stent assembly deployed at a defect site 20 within an artery. In the figure, the outer diameter of the stent assembly including the outer cladding 16 covering the outside of the tubular support 10 is in an unexpanded state. delivered to the defect site 20. The expansion range of the stent assembly is: when it is located on the defect site 20, the maximum diameter of the expanded stent assembly can expand the arterial tissue around the stent assembly to such an extent that the blood flow obstruction at the defect site can be eradicated Phenomenon.

Implantation of stent components into blood vessels can cause some internal diseases of blood vessels, such as injury of vascular tissues, restenosis, stenosis in stents, and excessive cell proliferation during the implantation of stent components. As mentioned above, at least one coating layer 12 includes therein at least one medicament introduced within the layer for the purpose of delivering the at least one medicament into the vasculature of the body for the treatment of the aforementioned diseases. Thus, the purpose of at least one covering layer 12 is not only for implanting the assembly on the artery, but also serves as a storage agent. The stored agent will be delivered to the vasculature over an extended period of time. Within the above diameter range, the larger the total volume of the at least one covering layer 12 is, the greater its ability to store medicine is.

In addition, the inner covering layer 14 and the outer covering layer 16 are preferably porous to accommodate the migration of cells from the surrounding tissue and to promote the proliferation of these cells.

FIG. 6 shows a partial view of a nonwoven web of polymer fibers used to form at least one cover layer 12. As shown in FIG. Fibers 22, 24, and 26 intersect and join together at the intersection points, the interstices thus created making the web highly porous. Nonwoven webs of polymeric fibers are produced using the electrospinning technique described in more detail below. The cladding obtained by this technique can be used to form graft elements with unique advantages. Because the electrospun fibers are ultrafine, they have an exceptionally large surface area, allowing large quantities of pharmaceutical agents to be introduced into them. The surface area of the electrospun polymer fibers is close to that of activated carbon, which makes the polymer fiber nonwoven web an effective topical drug delivery system. In addition, the porosity of the inner cladding layer 14 and the outer cladding layer 16 can be independently controlled to form a uniform distribution of voids with a predetermined size and direction, which can promote high tissue ingrowth and cell endothelialization. (cell endothelization).

Regardless of the technique used to embed the agent in the coating, the preferred mechanism for release of the agent from the at least one coating 12 is by diffusion. The duration of release of the therapeutic agent at a predetermined concentration depends on many factors, which can be controlled during the manufacturing process. One factor is the chemistry of the carrier polymer and the chemical means of attaching the agent to the carrier polymer. This factor can be controlled by appropriate selection of the polymer(s) used for electrospinning. Another factor is the contact area between the body and the agent, which can be controlled by varying the free surface of the electrospun polymer fibers. Affecting the duration of drug release is also a method of introducing the drug into the at least one coating layer 12, and this factor will be further described later.

According to a preferred embodiment of the invention, at least one cladding layer 12 comprises a plurality of "sub-layers". Depending on the function of these sublayers, their fiber orientation, polymer type, incorporated agent and desired agent release rate can all be different. Thus, drug release in the first hours and days after implantation of the stent assembly can be achieved by introducing a solid solution in the sublayer of easily soluble biodegradable polymer fibers, in which Contains agents such as anticoagulants and antithrombotics. Thus, during the first period after implantation, the released agents include anticoagulant and antithrombotic agents.

In FIG. 6 , the medicament may consist of particles 28 embedded within electrospun polymer fibers forming a sub-layer of at least one cladding layer 12 . This method is suitable for drug release in the first days and weeks after surgery. To this end, agents may include antibiotics or antibiotics, thrombolytics, vasodilators, and the like. The duration of the release process is influenced by the type of polymer from which the respective sublayer is made. In particular, the use of moderately stable biodegradable polymers ensures optimal release rates.

Figure 7 shows an alternative method of introducing a drug into at least one coating 12, which ensures release of the drug in the first days and weeks after surgery. According to a preferred embodiment of the invention, the agent consists of a plurality of compacts 30 distributed between the electrospun polymer fibers of at least one cladding layer 12 . In this preferred embodiment of the invention, compacts 30 may take any known form, such as, but not limited to, moderately stable biodegradable polymer capsules.

The present invention is also capable of providing drug release over months to years. According to this preferred embodiment of the invention, the medicament is dissolved or encapsulated in the corresponding sublayer, and the material from which the sublayer is made is a biostable fiber. The diffusion rate of the agent from the biostable sub-layer to the outside is very slow, thus ensuring the long-term effect of the agent release. Agents suitable for such long-term release include, for example, antiplatelet agents, growth factor antagonists, and free radical scavengers.

Thus, the sequence of agent release and the duration of drug effect of certain particular agents depends on the type of polymer into which the agent is incorporated, the method of incorporation of the agent into the electrospun polymer fibers, and the order of the various layers forming at least one coating layer 12. , the matrix morphology of each layer, and the concentration of the agent.

These critical factors are governed by the electrospinning fabrication method described here. Although electrospinning can be effectively used to generate large diameter cannulas, the nature of the electrospinning technique makes it difficult to efficiently generate small diameter products such as drug-containing polymer-coated stent components. Specifically, the fiber direction in the small-diameter cladding produced by electrospinning is mainly axial, which makes its radial strength significantly inferior to its axial strength.

In the process of putting the present invention into practice, we found that when the substantially thick and strong fibers are placed in the axial position and the substantially thin and elastic fibers are placed in the transverse direction (polar direction), The mechanical strength of the coating can be improved.

Accordingly, the present invention provides a method of making a bracket assembly. The method includes: electrospinning a first liquefied polymer onto an expandable tubular support 10 to coat the tubular support 10 with a first coating having a predetermined porosity; A medicament is incorporated into the first coating. As noted above, in some embodiments, the agent is mixed with the liquefied polymer prior to electrospinning, so that the step of introducing the agent into the first coating is performed simultaneously with the electrospinning step.

The electrospinning step can be performed using any electrospinning equipment known in the art. Referring now again to the accompanying drawings. A typical electrospinning apparatus is shown in FIG. 8 , which includes a pump 40 , a mandrel 42 connected to a power source 43 and a distribution electrode 44 . The pump 40 communicates with a bath 41 and is used to pump the liquid polymer stored in the bath 41 to the distribution electrode 44 through a syringe (not shown in FIG. 8 ). A first potential difference is maintained between the mandrel 42 and the distribution electrode 44, so that a first electric field is generated therebetween. According to the electrospinning method, after the liquefied polymer is drawn into the distribution electrode 44, it is charged and distributed in the direction of the mandrel 42 by the action of the first electric field. Fibers are formed and collected on the surface of the mandrel 42 as the jet of liquefied polymer cools as it travels at high speed in the interelectrode space or the solvent therein evaporates.

Figure 9 shows the electrospinning apparatus used to fabricate another preferred embodiment of the stent assembly of the present invention. The method may also include providing a second electric field bounded by an auxiliary electrode 46 maintained at a second potential difference relative to the mandrel 42 . The function of the second electric field (and the auxiliary electrode 46 ) is to modify the first electric field, so as to ensure a predetermined fiber orientation when forming the cladding layer. In order to manufacture a stent assembly having all the above-mentioned structural features, it is very important to obtain the predetermined fiber direction.

There are two possible approaches in making the outer cladding 16 of the tubular support 10 . The first is to mount the tubular support 10 on the mandrel 42 before electrospinning, and the second is to use the tubular support 10 itself as the mandrel.

In the preferred embodiment, the tubular support 10 is supported by the mandrel 42, which may act as a metal electrode to which a high voltage is applied to establish an electric field. The polymer fibers then emerge from the distribution electrode 44 and shoot towards the mandrel 42 to form the outer cladding 16 on the tubular support 10 . Such cladding covers both the wires of the tubular support 10 and the wires and the gaps between the wires.

In other embodiments, the outer cladding 16 exposes the wire-to-wire gaps, but only covers the wires of the tubular support 10 . This can be achieved either by using the tubular support 10 itself as the mandrel, or by making the mandrel out of an insulating material instead of a conductive material. According to this embodiment of the invention, the metal mesh of the tubular support 10 acts as an electrode and is connected to a high voltage power source to create an electrostatic field that extends only to the stent and not to the mandrel (in a preferred embodiment scheme, a mandrel of insulating material is used). In this way, the polymer fibers are only attached to the wires of the tubular support 10, exposing the gaps between the wires. In either case, the resulting polymer-coated stent is microporous to facilitate delivery of agents from the stent assembly into the body's vasculature.

According to a preferred embodiment of the present invention, the method further includes providing an inner cladding 14 lining the inner surface of the tubular support 10 . Thus, according to this preferred embodiment of the invention, the inner cladding 14 is first produced by electrospinning cladding directly on the mandrel 42 . Once the mandrel 42 is coated, the electrospinning is paused and the tubular support 10 is slid onto the mandrel and dragged onto the inner cladding 14, and the electrospinning process is resumed on the tubular support 10. Spun to make the outer cover 16 .

Because the inner cladding layer 14 is required to be stopped for a period of time after it is made, most of the solvent in the cladding layer 14 may evaporate during this pause. A weak bond between the two elements of the stent assembly may result when the next step is repeated, and delamination of the coating may occur when the stent-graft is unfolded.

The present invention successfully solves the above-mentioned disadvantages through two optimization techniques. According to one of the techniques, the outer sublayer of the inner cladding layer 14 and the inner sublayer of the outer cladding layer 16 are each formed from high performance electrospun layers. Typical ranges for performance improvements are between about 50% and about 100%. This technique produces a dense adhesive layer with coarser fibers and significantly increased solvent content. Typical thicknesses of the adhesive layer range from about 20 microns to about 30 microns. This thickness is small compared to the overall diameter of the stent assembly and therefore does not significantly affect the overall performance of the cladding. According to an alternative technique, the adhesive layer comprises an alternative polymer. The surrogate polymer has a lower molecular weight and higher elasticity and reactivity than the base polymer.

In order to improve the adhesion between the various layers and the tubular support 10, other techniques may also be used. For example, various adhesives, primers, solders, chemical connections in solvent vapor, etc. may be used. Examples of suitable materials include silanes such as aminoethylaminopropyl-triacylsilane.

The advantage of using electrospinning technology to make at least one cladding layer 12 is that the type of polymer and the thickness of the fibers can be freely selected, so that the final product made can have the required strength, elasticity and other properties mentioned above. Comprehensive performance. In addition, forming at least one cladding layer 12 in an alternating sequence of multiple sub-layers, wherein each sub-layer is made with fibers of different orientations, determines the distribution characteristics of the void ratio along the wall thickness of the stent assembly. In addition, another benefit of electrospinning technology is that various chemical components to be introduced into fibers, such as pharmaceuticals, can be mixed into the liquefied polymer before electrospinning.

Figure 10 shows an electrospinning apparatus used to fabricate a scaffold assembly according to another preferred embodiment of the present invention. In this embodiment of the invention, the agent is mixed with the liquefied polymer in bath 52 prior to electrospinning. The resulting mixture is delivered by a pump 50 to an electrostatic sprayer 54 for spraying onto a tubular support 10 (not shown) mounted on the mandrel 42 . Preferably, axially oriented fibers that do not substantially contribute to radial strength may be fabricated from biodegradable polymers and loaded with agents therein. Such a manner of introducing the agent will allow for a slow release of the agent during the biodegradation of the fiber. The agent may be mixed into the liquefied polymer by any suitable method, for example by dissolution or suspension. The medicament may consist of granules or may be in a dissolved state.

In a preferred embodiment, the medicament is intended to be trapped in the interstices of the nonwoven web of the at least one covering layer 12 . The medicament is preferably in the form of a powder or microcapsules, so that the medicament can be sprayed onto a particular layer of the at least one coating 12 once it has been formed in particle clusters.

Figure 11 shows the electrospinning apparatus used in accordance with this preferred embodiment of the invention. A biocompatible agent is drawn from supply 58 and supplied to electrostatic sprayer 56 . The medicament is sprayed towards the bracket assembly in the form of a spray of medicament particles through a conical deflector 60 .

It should be noted that although the present invention has been specifically described herein in connection with a tubular support 10, various other medical implants that do not necessarily have to be in a tubular configuration may also be coated with the techniques of the present invention. Grafts and patches, for example, can be coated and medicated prior to implantation or application, thereby having the various benefits described herein.

The at least one covering layer 12 can be made of any known biocompatible polymeric material. In the layers incorporating the medicament, the polymeric fibers are preferably a combination of biodegradable and biostable polymers.

Biostable polymers with relatively low long-term tissue response include aliphatic polyurethanes of the polycarbonate type, aromatic polyurethanes of the silicone type, polydimethylsiloxane, and others. Silicone rubber, polyesters, polyolefins, polymethyl methacrylates, vinyl halide polymers and copolymers, polyvinyl aromatic compounds, polyvinyl esters, polyamides, polyimides, polyethers, and many others can be dissolved in suitable other polymers in a solvent and electrospun onto the scaffold.

Suitable biodegradable fiber-forming polymers include poly(L-lactic acid), poly(lactide-co-glycolide), polycaprolactone, polyphosphite, poly(hydroxy-butyrate), Poly(glycolic acid), poly(DL-lactic acid), poly(amino acids), cyanoacrylates, certain copolymers and biomolecules such as DNA, silk, polyglucosamine and cellulose.

These hydrophilic or hydrophobic polymers, which are easily degraded by microorganisms and enzymes, are very suitable for making pharmaceutical capsules. Polycaprolactone, in particular, has a slower degradation rate than most other polymers and is therefore particularly suitable for long-term controlled release of medicaments for as long as about 2 to about 3 years.

Agents suitable for incorporation into at least one coating layer 12 may include heparin, tris(lauryl)methylammonium-heparin, epothilone A, epothilone B, epothilone C, ticlopil Dexamethasone, caumadin, and other agents usually selected from the following classes of agents: antithrombotics, estrogens, corticosteroids, cytostatics, anticoagulants, vasodilators, antiplatelets, thrombolytics , antimicrobials or antibiotics, antimitotics, antiproliferative, antisecretory, nonsteroidal anti-inflammatory drugs, growth factor antagonists, free radical scavengers, antioxidants, radiopaque agents, immunosuppressants, and radiation Marking agent.

Those skilled in the art will have a clearer understanding of other objectives, benefits and new features of the present invention after reading the examples to be described below. These examples do not limit the scope of the invention. In addition, the various embodiments and contents referred to in the foregoing and claims of the present invention are experimentally supported in the examples to be described below.

Example

Reference is now made to the following examples which, together with the foregoing description, serve only as non-limiting illustrations of the invention.

                                   

The cladding was made with Carbothane PC-3575 sold by Thermedics Polymer Products. The polymer has desirable fiber-forming capabilities and is a biocompatible polymer with lipophilic agent incorporation capabilities. The solvent used in all experiments was a mixture of dimethylformamide and toluene, where the ratio of dimethylformamide to toluene ranged from 1:1 to 1:2.

Electrospinning was performed using a PHD 2000 syringe pump sold by Harvard Apparatus. The distribution electrode was a spinneret with an inner diameter of 0.9 mm. The spinning rate of the spinneret is between 0.05 ml/min and 5 ml/min. The mandrel potential was maintained at about 20-50 kV, while the distribution electrode was grounded. The mandrel is made of polished stainless steel and its speed is 100-150 rpm.

The distance between the distribution electrode and the deposition electrode is about 25 to 35 cm. The distribution electrode is connected to the pump with flexible Teflon tubing. The distributing electrode reciprocates along the axial direction of the mandrel with a stroke of 30 to 40 mm, and the reciprocating frequency is 2-3 times/minute.

Example 1

The length of the bracket assembly is 16mm. The tubular support in the stent assembly was a stainless steel stent with a diameter of 3 mm in the expanded state and 1.9 mm in the non-expanded state. The stainless steel stents used are commonly used in catheter and balloon angioplasty. To improve the adhesion quality of the polymer coating, the stent was exposed to a corona discharge of 160–180 kJ/ ^m2 , rinsed with ethanol and deionized water and dried in a nitrogen stream. The concentration of the solution was 8%; the viscosity was 560 centipoise; the conductance was 0.8 microSiemens. The medicament used is a tetrahydrofuran solution of heparin with a concentration of 250 units/ml. The ratio of polymer to heparin solution was 100:1. The mandrel is a metal rod with a diameter of 1.8 mm and a length of 100 mm.

In order to ensure the uniform and high-quality coating of the electrode with small curvature radius, a planar auxiliary electrode is set near the mandrel at a distance of 40 mm from the mandrel axis, and the potential of the auxiliary electrode is basically equal to that of the mandrel.

The cladding process is divided into two steps. First, a layer of polymer fibers about 40 microns thick was electrospun on a mandrel. Once the first step is completed, the tubular support is placed on the first cladding, thus obtaining the inner cladding of the tubular support. Second, an outer cladding with a thickness of about 100 microns is formed on the outer surface of the tubular support.

Then the bracket assembly was removed from the mandrel, and placed in a DMF saturated steam atmosphere at a temperature of 45° C. for about 30 seconds to ensure high-quality bonding strength between the inner and outer cladding layers. Finally, to remove residual solvent, the scaffold assembly was exposed to partial vacuum for about 24 hours.

Example 2

The manufacture of the bracket assembly is as in Example 1. However, the agent is a mixture of heparin and 15% poly(DL-lactide-CD-glycolide) in chloroform, the concentration of heparin being 380 units/ml.

Additionally, distribution electrodes are used. Two electrodes were electrospun simultaneously. One electrode is mounted on top of the other with a height difference of 20 mm. The first electrode was used to spin polyurethane, while the other simultaneously spun the biodegradable polymer poly(L-lactic acid). In order to ensure the proper ratio between polyurethane and biodegradable polymer fiber volumes, the solution supply flow rate was 0.1 ml/min for the first spinneret and 0.03 ml/min for the second spinneret .

Example 3

The manufacturing material of bracket assembly is the same as example 1.

The coating process is carried out in two steps. In the first step, a coating of polymer fibers with a thickness of about 60 microns is produced by electrospinning on a mandrel. Once the first step is completed, the tubular support is placed on the first cladding, thus obtaining the inner cladding of the tubular support. A 120 mm diameter annular auxiliary electrode was fitted 16 mm behind the mandrel prior to the fabrication of the outer cladding.

Auxiliary electrodes were fabricated from 1 mm thick wire. The coupling plane of the auxiliary electrode is perpendicular to the longitudinal axis of the mandrel. As in Example 1, the potential of the auxiliary electrode and the spindle potential are substantially equal; however, unlike Example 1, the auxiliary electrode and spinneret are mechanically and dynamically linked together so that they are displaced synchronously.

The making of the second cladding layer is the same as in Example 1, until the total thickness of the cladding layer reaches 100 microns.

Experiments have shown that the main direction of the heparin-loaded biodegradable polymer fibers is aligned with the longitudinal axis of the mandrel, while the main direction of the polyurethane fibers is transverse (polar direction).

Example 4

The bracket assembly was fabricated as in Example 1. And the polymer solution is added with aspirin powder. The root mean square (RMS) diameter of the particles is equal to 0.2 microns. The mass content of the powder in the solution accounts for 3.2% of the dry polymer (dry polymer) mass. In order to obtain a stable suspension, the mixture was mixed for 6 hours with a magnetic stirrer sold by Freed electric and intermittently (1:60) applied with 32 kHz ultrasonic waves generated by the PUC40 device.

Example 5

The scaffold assembly was fabricated as in Example 3, but the solution used was of higher viscosity (up to 770 centipoise) and higher conductance (2 microSiemens). Solutions with such characteristics help to produce thicker fibers and thinner fabric structures.

In addition, the aspirin is delivered to a fluidized bed and then to the spinneret. Jetting and electrospinning were performed simultaneously in intermittent mode: 5 seconds of jetting followed by a 60 second break. The potential difference between the distribution electrodes and the mandrel was 23 kV, the distance between the electrodes was 15 cm, and the powder supply rate was 100 mg/min.

Example 6

A stent assembly with an inner cladding and an outer cladding was fabricated using the methods described herein. The outer coating was made from a polymer solution having the parameters listed in Example 4, but with only the heparin solution added as described in Example 3. The inner cladding of the stent was fabricated from a polymer solution with the parameters listed in Example 1, but only with heparin solution as described in Example 3. Thus, the inner cladding is characterized by fine fibers and pores with a size of about 1 micron. This characteristic coating ensures effective surface endodermalization. The outer surface then has micropores with a size of about 5-15 microns to allow for tissue ingrowth.

Example 7

The bracket assembly was fabricated as in Example 1. However, the drug introduced into the inner and outer coating layers is not heparin but a chloroform solution containing 6% ratamycine.

Example 8

The bracket assembly was fabricated as in Example 1. However, the medicament introduced in the outer coating layer is not heparin but a chloroform solution of ticlopidine, and the inner coating layer is made as in Example 1.

Example 9

The manufacturing material of bracket assembly is the same as example 1. But before electrospinning coating, the scaffold was dipped in 1-MP solution of TECOFLEX adhesive. In addition, the distance between the auxiliary electrode and the mandrel was reduced to 20 mm. In addition, the step of working up in solvent vapor was omitted.

The purpose of this example was to create an outer cladding that only covered the wires of the tubular support, exposing the gaps between the wires. Therefore, the mandrel used is made of insulating material, while the tubular support is maintained at a potential of 25 kV by means of electrical contacts.

Although the invention has been described in detail in connection with specific embodiments, it will be apparent to those skilled in the art that many alternatives can be devised or modifications and variations of these embodiments can be devised. Accordingly, it is intended to include in the claims all such alternatives, modifications and variations within the spirit and scope of the invention.

All publications, patents, and patent applications mentioned in this specification are hereby incorporated by reference in their entirety, as specifically and individually indicated in all such publications, patents, and patent applications. In addition, any citation or identification of these references in this application shall not be construed as an admission by the applicants that prior art exists with respect to the present invention.

Claims (229)

1. A stent assembly comprising an expandable tubular support and at least one electrospun polymer fiber coating, each of said at least one coating having a predetermined porosity, the At least one coating layer includes at least one agent incorporated within the layer for delivery of the at least one agent into the body's vasculature when or after the stent assembly is implanted in the body's vasculature. 2. The stent assembly of claim 1, wherein said expandable tubular strut is designed and configured to dilate a narrowed blood vessel within the vasculature of said body. 3. The stent assembly of claim 1, wherein each of said at least one cladding layer is independently a tubular structure. 4. The stent assembly of claim 2, wherein said at least one medicament is used to treat at least one disease within said blood vessel. 5. The stent assembly of claim 4, wherein said at least one disease comprises damage to said vascular tissue during implantation of the stent assembly. 6. The stent assembly of claim 4, wherein said at least one disease is selected from restenosis and in-stent stenosis. 7. The scaffold assembly of claim 4, wherein said at least one disease is cellular hyperproliferation. 8. The stent assembly of claim 1, wherein said at least one coating layer and at least one agent are constructed and designed to provide a predetermined sustained release rate of the agent to effectuate said delivery. 9. The stent assembly of claim 1, wherein said at least one coating and at least one agent are constructed and designed to provide said delivery for a predetermined duration. 10. The stent assembly of claim 1, wherein said delivery is by means of diffusion. 11. The stent assembly of claim 10, wherein said delivery begins with radial expansion of said at least one cladding layer caused by expansion of said expandable tubular strut. 12. The stent assembly of claim 1, wherein said expandable tubular support comprises a deformable wire mesh. 13. The stent assembly of claim 1, wherein said expandable tubular support comprises a deformable stainless steel wire mesh. 14. The stent assembly of claim 1, wherein said at least one cladding layer comprises an inner cladding layer and an outer cladding layer. 15. The stent assembly of claim 14, wherein said inner cladding comprises a layer lining the inner surface of said expandable tubular support. 16. The stent assembly of claim 14, wherein said outer covering comprises a layer overlying an outer surface of said expandable tubular support. 17. The stent assembly of claim 1, wherein said electrospun polymer fibers are made of a biocompatible polymer. 18. The stent assembly of claim 1, wherein at least a portion of said electrospun polymeric fibers are made of a biodegradable polymer. 19. The stent assembly of claim 1, wherein at least a portion of said electrospun polymeric fibers are made of a biostable polymer. 20. The stent assembly of claim 1, wherein at least a portion of said electrospun polymeric fibers are made from a combination of biodegradable and biostable polymers. 21. The stent assembly of claim 1, wherein said electrospun polymer fibers are made from a liquefied polymer. 22. The stent assembly of claim 21, wherein said at least one agent is dissolved in said liquefied polymer. 23. The stent assembly of claim 21, wherein said at least one pharmaceutical agent is suspended in said liquefied polymer. 24. The stent assembly of claim 1, wherein said at least one agent consists of a compact distributed between said electrospun polymer fibers of said at least one cladding layer. 25. The stent assembly of claim 24, wherein said compact is a capsule. 26. The stent assembly of claim 1, wherein said at least one agent consists of particles embedded in said electrospun polymer fibers. 27. The stent assembly of claim 1, wherein said at least one covering layer comprises an adhesive layer. 28. The stent assembly of claim 27, wherein said adhesive layer is an impermeable adhesive layer. 29. The stent assembly of claim 27, wherein the adhesive layer is formed from electrospun polymer fibers. 30. The stent assembly of claim 1, wherein the electrospun polymer fibers are selected from the group consisting of polyethylene terephthalate fibers and polyurethane fibers. 31. The stent assembly of claim 1, wherein said at least one agent comprises heparin or a derivative of heparin. 32. The stent assembly of claim 1, wherein said at least one agent comprises a radioactive compound. 33. The stent assembly of claim 1, wherein said at least one agent comprises silver sulfadiazine. 34. The stent assembly of claim 1, wherein said at least one pharmaceutical agent comprises an antiproliferative agent. 35. The stent assembly of claim 1, wherein said at least one agent comprises an anti-aggregation agent. 36. The stent assembly of claim 12, wherein said at least one coating covers only said wires exposing gaps between said wires. 37. The stent assembly of claim 12, wherein said at least one coating substantially covers not only said wires but also spaces between said wires. 38. A method of manufacturing a stent assembly, the method comprising: (a) electrospinning a first liquefied polymer onto an expandable tubular support such that the tubular support is covered with a first coating having a predetermined porosity; and (b) introducing at least one medicament into said first coating layer. 39. The method of claim 38, wherein said at least one medicament is mixed with said liquefied polymer prior to electrospinning, whereby said process of introducing said at least one medicament into said first coating layer The steps are carried out simultaneously with the electrospinning process. 40. The method of claim 39, wherein said at least one agent is dissolved in said liquefied polymer. 41. The method of claim 39, wherein said at least one agent is suspended in said liquefied polymer. 42. The method of claim 39, wherein said at least one agent consists of particles embedded in polymer fibers produced by an electrospinning process. 43. The method of claim 38, wherein said step of introducing at least one medicament into said first coating comprises forming said at least one medicament into a compact, and distributing the compact to the Between the polymer fibers produced by the above electrospinning step. 44. The method of claim 43, wherein said compact is a capsule. 45. The method of claim 43, wherein said compact is in powder form. 46. The method of claim 43, wherein distribution of the compact is performed by spraying. 47. The method of claim 38, wherein said expandable tubular support comprises a deformable wire mesh. 48. The method of claim 38, wherein said expandable tubular support comprises a deformable stainless steel wire mesh. 49. The method of claim 38, wherein said cladding is of tubular construction. 50. The method of claim 38, further comprising mounting said tubular support onto a rotating mandrel prior to step (a). 51. The method of claim 50, further comprising electrospinning a second liquefied polymer onto said mandrel to form an inner cladding prior to step (a). 52. The method of claim 38, further comprising electrospinning at least one additional liquefied polymer onto said first coating, thereby forming at least one additional coating. 53. The method of claim 38, further comprising forming at least one adhesive layer on said tubular support. 54. The method of claim 51, further comprising forming at least one adhesive layer on at least one coating layer. 55. The method of claim 53, wherein said adhesive layer is an impermeable adhesive layer. 56. The method of claim 54, wherein said adhesive layer is an impermeable adhesive layer. 57. The method of claim 53, wherein said forming at least one adhesive layer is performed by electrospinning. 58. The method of claim 54, wherein said forming at least one adhesive layer is performed by electrospinning. 59. The method of claim 50, wherein the electrospinning step comprises: (a) charging said liquefied polymer, thereby producing a charged liquefied polymer; (b) placing said charged liquefied polymer in a first electric field; and (c) distributing the charged liquefied polymer in the first electric field along the direction of the mandrel. 60. The method of claim 59, wherein said mandrel is an electrically conductive material. 61. The method of claim 60, wherein said first electric field is defined between said mandrel and a distribution electrode at a first potential relative to said mandrel. 62. The method of claim 60, further comprising generating a second electric field bounded by an auxiliary electrode at a second potential relative to said mandrel, the second electric field being The purpose is to correct the first electric field. 63. The method of claim 62, wherein the purpose of the auxiliary electrode is to reduce non-uniformity of the first electric field. 64. The method of claim 62, wherein said auxiliary electrodes are used to control the fiber orientation of each of said cladding layers. 65. The method of claim 59, wherein said mandrel is an insulating material. 66. The method of claim 59, wherein said tubular support is used as a mandrel. 67. The method of claim 65, wherein said first electric field is defined between said tubular support and a distribution electrode at a first potential relative to said tubular support. 68. The method of claim 65, further comprising generating a second electric field defined by an auxiliary electrode at a second potential relative to said tubular support, said second The purpose of the electric field is to modify the first electric field. 69. The method of claim 68, wherein the purpose of the auxiliary electrode is to reduce non-uniformity of the first electric field. 70. The method of claim 68, wherein said auxiliary electrodes are used to control the fiber orientation of each of said cladding layers. 71. The method of claim 38, wherein said first liquefied polymer is a biocompatible liquefied polymer. 72. The method of claim 38, wherein said first liquefied polymer is a biodegradable liquefied polymer. 73. The method of claim 38, wherein said first liquefied polymer is a biostable liquefied polymer. 74. The method of claim 38, wherein said first liquefied polymer is a combination of a biodegradable liquefied polymer and a biostable liquefied polymer. 75. The method of claim 51, wherein said second liquefied polymer is a biocompatible liquefied polymer. 76. The method of claim 51, wherein said second liquefied polymer is a biodegradable liquefied polymer. 77. The method of claim 51, wherein said second liquefied polymer is a biostable liquefied polymer. 78. The method of claim 51, wherein said second liquefaction polymer is a combination of a biodegradable liquefaction polymer and a biostable liquefaction polymer. 79. The method of claim 52, wherein each of said at least one additional liquefied polymer is independently a biocompatible liquefied polymer. 80. The method of claim 52, wherein said at least one additional liquefied polymer is each independently a biodegradable liquefied polymer. 81. The method of claim 52, wherein said at least one additional liquefied polymer is each independently a biostable liquefied polymer. 82. The method of claim 52, wherein said at least one additional liquefaction polymer is each independently a combination of a biodegradable liquefaction polymer and a biostable liquefaction polymer. 83. The method of claim 38, wherein said at least one agent is heparin. 84. The method of claim 38, wherein said at least one agent is a radioactive compound. 85. The method of claim 38, wherein said at least one agent is silver sulfadiazine. 86. The method of claim 50, further comprising heating the mandrel before, during, or after the electrospinning step. 87. The method of claim 86, wherein said heating of said mandrel is selected from external heating and internal heating. 88. The method of claim 87, wherein said external heating is performed by at least one infrared radiator. 89. The method of claim 88, wherein said at least one infrared radiator is an infrared light bulb. 90. The method of claim 87, wherein said internal heating is performed by a built-in heater. 91. The method of claim 90, wherein said built-in heater is a built-in resistive heater. 92. The method of claim 50, further comprising removing the stent assembly from the mandrel. 93. The method of claim 92, further comprising immersing the stent assembly in vapor. 94. The method of claim 93, further comprising heating the vapor. 95. The method of claim 92, wherein said vapor is a saturated DMF vapor. 96. The method of claim 38, further comprising exposing the stent assembly to a partial vacuum for processing. 97. A method of treating a narrowed blood vessel, the method comprising deploying a stent assembly comprising an expandable tubular strut and at least one coating of electrospun polymeric fibers into the narrowed blood vessel , each of said at least one cladding layer has a predetermined porosity, said at least one cladding layer comprising at least one medicament introduced into the layer for the purpose of implanting the stent assembly in the vasculature of the body Or after implantation, the at least one agent is delivered into the vasculature of the body. 98. The method of claim 97, wherein said expandable tubular support is designed and configured to dilate a narrowed blood vessel within the vasculature of said body. 99. The method of claim 97, wherein each of said at least one cladding layer is independently a tubular structure. 101. The method of claim 98, wherein said at least one agent is used to treat at least one disease within said blood vessel. 101. The method of claim 100, wherein said at least one disease comprises damage to said vascular tissue during implantation of a stent assembly. 102. The method of claim 100, wherein said at least one disease is selected from restenosis and in-stent stenosis. 103. The method of claim 100, wherein said at least one disease is cellular hyperproliferation. 104. The method of claim 97, wherein said at least one coating and at least one agent are constructed and designed to provide a predetermined sustained release rate of the agent to effectuate said delivery. 105. The method of claim 97, wherein said at least one coating and at least one agent are constructed and designed to provide said delivery for a predetermined duration. 106. The method of claim 97, wherein said delivering is by means of diffusion. 107. The method of claim 106, wherein said delivering begins with radial expansion of said at least one coating layer caused by expansion of said expandable tubular support. 108. The method of claim 97, wherein said expandable tubular support comprises a deformable wire mesh. 109. The method of claim 97, wherein said expandable tubular support comprises a deformable stainless steel wire mesh. 110. The method of claim 97, wherein said at least one cladding layer comprises an inner cladding layer and an outer cladding layer. 111. The method of claim 110, wherein said inner cladding comprises a layer lining the inner surface of said expandable tubular support. 112. The method of claim 110, wherein said outer cladding comprises a layer covering an outer surface of said expandable tubular support. 113. The method of claim 97, wherein said electrospun polymer fibers are made of a biocompatible polymer. 114. The method of claim 97, wherein at least a portion of said electrospun polymeric fibers are made of a biodegradable polymer. 115. The method of claim 97, wherein at least a portion of said electrospun polymer fibers are made of a biostable polymer. 116. The method of claim 97, wherein at least a portion of said electrospun polymeric fibers are made from a combination of biodegradable and biostable polymers. 117. The method of claim 97, wherein said electrospun polymeric fibers are made from liquefied polymers. 118. The method of claim 117, wherein said at least one agent is dissolved in said liquefied polymer. 119. The method of claim 117, wherein said at least one agent is suspended in said liquefied polymer. 120. The method of claim 97, wherein said at least one agent consists of a compact distributed between said electrospun polymer fibers of said at least one cladding layer. 121. The method of claim 120, wherein said compact is a capsule. 122. The method of claim 97, wherein said at least one agent consists of compacts embedded in said electrospun polymer fibers. 123. The method of claim 97, wherein said at least one covering layer comprises an adhesive layer. 124. The method of claim 123, wherein said adhesive layer is an impermeable adhesive layer. 125. The method of claim 123, wherein the adhesive layer is formed from electrospun polymeric fibers. 126. The method of claim 97, wherein said electrospun polymer fibers are selected from polyethylene terephthalate fibers and polyurethane fibers. 127. The method of claim 97, wherein said at least one agent comprises heparin or a derivative of heparin. 128. The method of claim 97, wherein said at least one agent comprises a radioactive compound. 129. The method of claim 97, wherein said at least one agent comprises silver sulfadiazine. 130. The method of claim 97, wherein said at least one agent comprises an antiproliferative agent. 131. The method of claim 97, wherein said at least one agent comprises an anti-aggregating agent. 132. The method of claim 108, wherein said at least one cladding layer covers only said wires exposing gaps between said wires. 133. The method of claim 108, wherein said at least one cladding substantially covers not only said wires but also gaps between said wires. 134. A method for widening and constricting blood vessels, the method comprising: (a) providing a scaffold assembly comprising an expandable tubular support and at least one coating of electrospun polymer fibers, each of said at least one coating having a predetermined void ratio, the at least a coating layer comprising at least one agent incorporated within the layer; (b) deploying the stent assembly into the constricted region within the constricted vessel; and (c) radially expanding the stent assembly within the vessel to expand the constricted region and allow blood flow through the vessel. 135. The method of claim 134, wherein the expandable tubular support is designed and configured to dilate narrowed blood vessels within the vasculature of the body. 136. The method of claim 134, wherein each of said at least one cladding layer is independently a tubular structure. 137. The method of claim 135, wherein said at least one agent is used to treat at least one disease within said blood vessel. 138. The method of claim 137, wherein said at least one disease comprises damage to said vascular tissue during implantation of a stent assembly. 139. The method of claim 137, wherein said at least one disease is selected from restenosis and in-stent stenosis. 140. The method of claim 137, wherein said at least one disease is cellular hyperproliferation. 141. The method of claim 134, wherein said at least one coating and at least one agent are constructed and designed to provide a predetermined sustained release rate of the agent to effectuate said delivery. 142. The method of claim 134, wherein said at least one coating and at least one agent are constructed and designed to provide said delivery for a predetermined duration. 143. The method of claim 134, wherein said delivering is by means of diffusion. 144. The method of claim 143, wherein said delivering begins with radial expansion of said at least one coating layer caused by expansion of said expandable tubular support. 145. The method of claim 134, wherein said expandable tubular support comprises a deformable wire mesh. 146. The method of claim 134, wherein said expandable tubular support comprises a deformable stainless steel wire mesh. 147. The stent assembly of claim 134, wherein said at least one cladding layer comprises an inner cladding layer and an outer cladding layer. 148. The stent assembly of claim 147, wherein said inner cladding comprises a layer lining an inner surface of said expandable tubular support. 149. The method of claim 147, wherein said outer cladding comprises a layer covering an outer surface of said expandable tubular support. 150. The method of claim 134, wherein said electrospun polymer fibers are made of a biocompatible polymer. 151. The method of claim 134, wherein at least a portion of the electrospun polymeric fibers are made of a biodegradable polymer. 152. The method of claim 134, wherein at least a portion of said electrospun polymer fibers are made of a biostable polymer. 153. The method of claim 134, wherein at least a portion of the electrospun polymeric fibers are made from a combination of biodegradable and biostable polymers. 154. The method of claim 134, wherein said electrospun polymeric fibers are made from liquefied polymers. 155. The method of claim 154, wherein said at least one agent is dissolved in said liquefied polymer. 156. The method of claim 154, wherein said at least one agent is suspended in said liquefied polymer. 157. The method of claim 134, wherein said at least one agent consists of a compact distributed between said electrospun polymeric fibers of said at least one cladding layer. 158. The method of claim 157, wherein said compact is a capsule. 159. The method of claim 134, wherein said at least one agent consists of particles embedded in said electrospun polymer fibers. 160. The method of claim 134, wherein said at least one coating layer comprises an adhesive layer. 161. The method of claim 160, wherein said adhesive layer is an impermeable adhesive layer. 162. The method of claim 160, wherein the adhesive layer is formed from electrospun polymeric fibers. 163. The method of claim 134, wherein the electrospun polymeric fibers are selected from the group consisting of polyethylene terephthalate fibers and polyurethane fibers. 164. The method of claim 134, wherein said at least one agent comprises heparin or a derivative of heparin. 165. The method of claim 134, wherein said at least one agent comprises a radioactive compound. 166. The method of claim 134, wherein said at least one agent comprises silver sulfadiazine. 167. The method of claim 134, wherein said at least one agent comprises an antiproliferative agent. 168. The method of claim 134, wherein said at least one agent comprises an anti-aggregation agent. 169. The method of claim 145, wherein said at least one cladding layer covers only said wires exposing gaps between said wires. 170. The method of claim 145, wherein said at least one cladding substantially covers not only said wires but also gaps between said wires. 171. A method of coating an implantable medical implant and loading a pharmaceutical agent into the medical implant, the method comprising: (a) electrospinning a first liquefied polymer onto the medical implant, thereby forming a first coating having a predetermined porosity on the medical implant; and (b) introducing at least one medicament into said first coating layer; Thus a medical implant coated and loaded with at least one medicament is obtained. 172. The method of claim 171, wherein said medical implant is selected from the group consisting of grafts, patches, and valves. 173. The method of claim 171, wherein said at least one medicament is mixed with a liquefied polymer prior to said electrospinning step, whereby said step of introducing said at least one medicament into said first coating layer and said The electrospinning steps are performed simultaneously. 174. The method of claim 173, wherein said at least one agent is dissolved in said first liquefied polymer. 175. The method of claim 173, wherein said at least one agent is suspended in said first liquefied polymer. 176. The method of claim 173, wherein said at least one agent consists of particles embedded in said electrospun polymer fibers. 177. The method of claim 171, wherein said step of introducing at least one agent into said first coating comprises forming said at least one agent into a compact, and distributing the compact to Between the polymer fibers produced by the above electrospinning step. 178. The method of claim 177, wherein said compact is a capsule. 179. The method of claim 177, wherein the compact is in powder form. 180. The method of claim 177, wherein distribution of the compacts is performed by spraying. 181. The method of claim 171, wherein the cladding is a tubular structure. 182. The method of claim 171, further comprising rotating said mandrel in said step (a). 183. The method of claim 182, wherein said rotating comprises coupling a medical implant to a rotating mandrel. 184. The method of claim 183, further comprising electrospinning a second liquefied polymer onto said mandrel prior to said step (a), thereby providing an inner cladding. 185. The method of claim 171, further comprising electrospinning at least one additional liquefied polymer onto said first coating, thereby providing at least one additional coating. 186. The method of claim 171, further comprising forming at least one adhesive layer on the medical implant. 187. The method of claim 184, further comprising forming at least one adhesive layer on at least one coating layer. 188. The method of claim 186, wherein said adhesive layer is an impermeable adhesive layer. 189. The method of claim 187, wherein said adhesive layer is an impermeable adhesive layer. 190. The method of claim 186, wherein said forming at least one adhesive layer is performed by electrospinning. 191. The method of claim 187, wherein said forming at least one adhesive layer is performed by electrospinning. 192. The method of claim 183, wherein the electrospinning step comprises: (i) charging the liquefied polymer to produce a charged liquefied polymer; (ii) placing the charged liquefied polymer in the first electric field; (iii) distributing the charged liquefied polymer in the direction of the mandrel in the first electric field. 193. The method of claim 192, wherein said mandrel is an electrically conductive material. 194. The method of claim 193, wherein said first electric field is defined between said mandrel and a distribution electrode at a first potential relative to said mandrel. 195. The method of claim 193, further comprising generating a second electric field determined by an auxiliary electrode at a second potential relative to said mandrel, the second electric field having The purpose is to correct the first electric field. 196. The method of claim 195, wherein the purpose of the auxiliary electrode is to reduce non-uniformity of the first electric field. 197. The method of claim 195, wherein said auxiliary electrode is used to control the fiber orientation of each of said coatings produced on a medical implant. 198. The method of claim 192, wherein said mandrel is an insulating material. 199. The method of claim 192, wherein said medical implant is used as a mandrel. 200. The method of claim 198, wherein said first electric field is defined between said medical implant and a distribution electrode at a first potential relative to said medical implant. 201. The method of claim 198, further comprising generating a second electric field bounded by an auxiliary electrode at a second potential relative to said medical implant, said second The purpose of the electric field is to modify the first electric field. 202. The method of claim 201, wherein the purpose of the auxiliary electrode is to reduce non-uniformity of the first electric field. 203. The method of claim 201, wherein said auxiliary electrode is used to control the fiber orientation of each of said coatings produced on a medical implant. 204. The method of claim 171, wherein said first liquefied polymer is a biocompatible liquefied polymer. 205. The method of claim 171, wherein said first liquefied polymer is a biodegradable liquefied polymer. 206. The method of claim 171, wherein said first liquefied polymer is a biostable liquefied polymer. 207. The method of claim 171, wherein said first liquefied polymer is a combination of a biodegradable liquefied polymer and a biostable liquefied polymer. 208. The method of claim 184, wherein said second liquefied polymer is a biocompatible liquefied polymer. 209. The method of claim 184, wherein said second liquefied polymer is a biodegradable liquefied polymer. 210. The method of claim 184, wherein said second liquefied polymer is a biostable liquefied polymer. 211. The method of claim 184, wherein said second liquefaction polymer is a combination of a biodegradable liquefaction polymer and a biostable liquefaction polymer. 212. The method of claim 185, wherein each of said at least one additional liquefied polymer is independently a biocompatible liquefied polymer. 213. The method of claim 185, wherein said at least one additional liquefied polymer is each independently a biodegradable liquefied polymer. 214. The method of claim 185, wherein said at least one additional liquefied polymer is each independently a biostable liquefied polymer. 215. The method of claim 185, wherein said at least one additional liquefaction polymer is each independently a combination of a biodegradable liquefaction polymer and a biostable liquefaction polymer. 216. The method of claim 171, wherein said at least one agent is heparin. 217. The method of claim 171, wherein said at least one agent is a radioactive compound. 218. The method of claim 171, wherein said at least one agent is silver sulfadiazine. 219. The method of claim 183, further comprising heating the mandrel before, during, or after the electrospinning step. 220. The method of claim 219, wherein said heating of said mandrel is selected from external heating and internal heating. 221. The method of claim 220, wherein said external heating is performed by at least one infrared radiator. 222. The method of claim 221, wherein said at least one infrared radiator is an infrared light bulb. 223. The method of claim 220, wherein said internal heating is performed by a built-in heater. 224. The method of claim 223, wherein said built-in heater is a built-in resistive heater. 225. The method of claim 183, further comprising removing the coated medical implant from the mandrel. 226. The method of claim 225, further comprising immersing the coated medical implant in steam. 227. The method of claim 226, further comprising heating the vapor. 228. The method of claim 225, wherein said vapor is a saturated DMF vapor. 229. The method of claim 171, further comprising exposing the coated medical implant to a partial vacuum.

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